肺癌轉移抑制基因—CRMP-1的上下游調控基因之分析(1/3)

Abstract

目前肺癌已是台灣以及世界各國最嚴 重的癌症死亡原因。癌轉移是目前外科 手術、放射治療、化學治療，各種治療 方法失敗的主要原因。我們希望研究癌 轉移機制，尋找與肺癌轉移有關的基 因，來改善治療的方法。利用已建立之 高侵襲及轉移傾向和低侵襲及轉移傾向之 各類腺癌細胞株(CL1-0, CL1-1, CL1-5, and CL1-F4)、cDNA 微陳列技術，找尋與 癌轉移相關之新基因。我們證實collapsin response mediator protein-1 (CRMP-1) 是一癌轉移抑制基因。之前學者已發現cyclooxygenase-2(COX-2)會促進癌轉移，促進癌細胞生長、抑制細胞凋亡，以及增加actinpolymerization ，進而增進細胞的活動力及 侵襲力，最終使癌細胞轉移。CRMP-1 與 COX-2 在許多方面，有著相反的功能。所 以我們想了解CRMP-1 與COX-2 之間的關係。初步的研究發現COX-2 表現會使CRMP-1 表現量減少；而加入COX-2 的抑 制劑，可使CRMP-1 表現增加。我們設計 一系列實驗來釐清CRMP-1 與COX-2 的交互作用。

Lung cancer is the leading cause of cancer mortality in most countries, including Taiwan. Metastasis is the most feared manifestation hat defeats the present modalities of treatments, such as surgery, radiation and chemotherapy. We are interested in studying specific mechanisms involving the metastasis in lung cancer and searching for new genes associated with the invasion of lung cancer, in order to improve the treatment modality. We used a high-density cDNA microarray to identify and then confirm CRMP-1 is an invasion-suppressor genes. Accumulating evidence has suggested that cancer cells expressing higher levels of COX-2 would obtain higher invasive abilities. CRMP-1 and COX-2 seem to work in opposite way. This study plans to investigate whether COX-2 would alter the cellular expression of CRMP-1 in human lung adenocarcinoma cell lines or vice versa. Preliminary results show that COX-2 inhibitor induces the expression of CRMP-1 and expression COX-2 suppresses the expression of CRMP-1.